Vascularized microfluidic platforms to mimic the tumor microenvironment.
Vascularized microfluidic platforms to mimic the tumor microenvironment.
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DOI：
10.1002/bit.26778
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发表时间：
2018-11
影响因子：
3.8
通讯作者：
Rylander M
中科院分区：
文献类型：
--
作者：
Michna R;Gadde M;Ozkan A;DeWitt M;Rylander M
微流控技术促进了先进体外肿瘤平台的发展，克服了体内动物和体外二维模型的挑战。本文介绍了用于开发复杂血管化体外模型以模拟肿瘤微环境的平台设计和方法。这些平台的特点包括连续、对齐的内皮细胞，允许脉管系统和肿瘤细胞之间的细胞间相互作用。开发了一种新平台，用于制造封装在容纳乳腺癌细胞的胶原平台内的单个内皮化微通道，并用于研究细胞相互作用对高渗透性肿瘤微环境中脉管系统运输现象的影响。该平台依赖于减材组织工程制造技术。通过共聚焦成像，我们证明该平台可产生增强的血管渗漏性，概括肿瘤微环境的生理特征。还证明了肿瘤内皮相互作用对颗粒运输的影响。此外，我们通过将光刻技术与增材组织工程方法相结合，设计了两个更复杂和复杂的内皮化微流体网络。我们创建了一个由互连微通道组成的网络平台来模拟高度血管化的系统，并成功地用荧光颗粒灌注该系统。最后，我们开发了一个具有生理代表性的体外微流体平台，其脉管系统根据体内数据进行建模，显示了这些系统的多功能性，可以复制肿瘤微脉管系统的复杂几何形状和动态测量的颗粒传输。总的来说，我们已经展示了开发不同复杂性的功能性微流体血管肿瘤平台的能力，并证明了它们在研究这些系统内的空间粒子传输方面的实用性。 3D 血管肿瘤微流体平台的开发，从单一血管到复杂的体内图案化血管平台。
Microfluidic technology has led to the development of advanced in vitro tumor platforms that overcome the challenges of in vivo animal and in vitro two dimensional models. This paper presents platform designs and methods used to develop complex vascularized in vitro models to mimic the tumor microenvironment. Features of these platforms include a continuous, aligned endothelium that allows for cell-cell interactions between vasculature and tumor cells. A novel platform for fabrication of a single endothelialized microchannel encased within a collagen platform hosting breast cancer cells was developed and utilized to study the influence of cellular interaction on transport phenomenon through vasculature in a hyperpermeable tumor microenvironment. This platform relies on subtractive tissue engineering fabrication techniques. Through confocal imaging we have demonstrated that the platform produces enhanced vessel leakiness recapitulating physiological features of the tumor microenvironment. The influence of tumor endothelial interactions on transport of particles was also demonstrated. Additionally, we designed two more complex and intricate endothelialized microfluidic networks by combining lithographic techniques with additive tissue engineering methods. We created a network platform consisting of interconnected microchannels to model a highly vascularized system and successfully perfused the system with fluorescent particles. Finally, we developed a physiologically representative in vitro microfluidic platform with vasculature patterned from in vivo data showing the versatility of these systems to replicate the complex geometries of tumor microvasculature and dynamically measured particle transport. Overall, we have shown the ability to develop functional microfluidic vascular tumor platforms of varying complexities and demonstrated their utility for studying spatial particle transport within these systems. Development of 3D vascular tumor microfluidic platforms from single vessel to complex in vivo patterned vascular platforms.
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影响因子：
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作者：
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通讯作者：
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